This research is designed to systematically evaluate the liposome as a drug delivery technique designed to improve the tissue selectivity, reduce the toxicity and increase the in vivo stability of a series of thiopurine nucleotides through alterations in the drug's pharmacokinetics and effective physical-chemical properties. We will determine which major liposome variable (size, charge, composition, etc.) contributes most to in vitro stability in various buffer and plasma solutions (instability is defined as liposome rupture, drug leakage or significant charges in sizes). The pharmacokinetic properties of various liposome types in normal rats to show which major liposome variable contributes most of liposome clearance from blood and relative drug delivery to liver, spleen, intestine, lung, kidney, brain and bone marrow as a function of time. The cyclic 3'-5' -phosphate of 6-mercaptopurineriboside has been used to prepare a series of 2'-O-acyl prodrugs of 6-mercaptopurine. We will show which major liposome variable contributes most to a decrease in the half-life of ester hydrolysis in buffer and plasma solutions. We will evaluate to what extent liposome encapsulation of prodrug 6-mercaptopurine nucleotides increases the effectiveness and degree of cellular incorporation of these drugs relative to the free prodrugs in vitro. Finally, we will seek answers to these questions: What is the practical upper limit for the amount of prodrug incorporated into a given liposome type? Will the observed pharmacokinetics be dependent on the properties of the encapsulated agents?